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Abstract

BACKGROUND:

People with severe hemophilia A or B, X-linked bleeding disorders due to decreased blood levels of coagulants, suffer recurrent bleeding into joints and soft tissues. Before clotting factor concentrates were available, most people with severe hemophilia developed crippling musculoskeletal deformities. Clotting factor concentrate prophylaxis aims to preserve joint function by converting severe hemophilia (factor VIII or IX less than 1%) into a clinically milder form of the disease. Prophylaxis has long been used in Sweden, but not universally adopted because of medical, psychosocial, and cost controversies. Use of clotting factor concentrates is the single largest predictor of cost in treating hemophilia.

OBJECTIVES:

To determine the effectiveness of clotting factor concentrate prophylaxis in the management of people with hemophilia A or B.

DATA COLLECTION AND ANALYSIS:

MAIN RESULTS:

Twenty-nine studies were identified, of which four (including 37 participants) were eligible for inclusion. Three studies evaluated hemophilia A; one showed a decrease in frequency of joint bleeds with prophylaxis compared to placebo (non-physiological dose), with a rate difference (RD) -10.80 (95% confidence interval (CI) -16.33 to -5.27) bleeds per year. The remaining two studies evaluating hemophilia A compared two prophylaxis regimens, one study showed no difference in joint bleed frequency, RD -5.04 (95%CI -17.02 to 6.94) bleeds per year and another failed to demonstrate an advantage of factor VIII dosing based on individual pharmacokinetic data over the standard prophylaxis regimen with RD -0.14 (95% CI -1.34 to 1.05) bleeds per year. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, RD -3.30 (95% CI -5.50 to - 1.10) bleeds per year.

AUTHORS' CONCLUSIONS:

There is insufficient evidence to determine whether prophylactic clotting factor concentrates decrease bleeding and bleeding-related complications in hemophilia A or B, compared to placebo, on-demand treatment, or prophylaxis based on pharmacokinetic data from individuals. Well-designed RCTs are needed to assess the effectiveness of prophylactic clotting factor concentrates. Two clinical trials are ongoing.